Synthesis and antibacterial activity of dihydro-1,2-oxazine and 2-pyrazoline oxazolidinones: novel analogs of linezolid

• Published in: Bioorganic & medicinal chemistry letters 2005-06, Vol.15 (11), p.2834-2839
• Main Authors: D’Andrea, Stan, Zheng, Zhizhen Barbara, DenBleyker, Kenneth, Fung-Tomc, Joan C., Yang, Hyekyung, Clark, Junius, Taylor, Dennis, Bronson, Joanne
• Format: Article
• Language: English
• Subjects: Acetamides - chemical synthesis; Acetamides - pharmacology; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antibacterial; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Gram-Positive Bacteria - drug effects; Linezolid; Medical sciences; Mice; Microbial Sensitivity Tests; Oxazoles - chemical synthesis; Oxazoles - pharmacology; Oxazolidinones; Oxazolidinones - chemical synthesis; Oxazolidinones - pharmacology; Pharmacology. Drug treatments
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.03.099

The synthesis and antibacterial activity of dihydro-1,2-oxazine and 2-pyrazoline oxazolidinones are reported. Dihydro-1,2-oxazine 6 and 2-pyrazoline 20 were found to have in vitro potencies rivaling linezolid. The synthesis and antibacterial activity of oxazolidinones containing dihydro-1,2-oxazine and 2-pyrazoline ring systems are described. Linezolid analogs utilizing dihydro-1,2-oxazines as morpholine mimics were prepared utilizing a nitrosoamine/diene 4+2 cycloaddition strategy. Pyrazolidine, hexahydro-pyridazine, and 2-pyrazoline analogs more closely related to eperezolid were also prepared. The most active of these new oxazolidinones were the dihydro-1,2-oxazine 6 and the 2-pyrazoline 20 both of which had potency similar to linezolid against a panel of Gram-positive bacteria.